过氧化物酶增殖物激活受体γ配体曲格列酮对大肠癌细胞生长的影响  

Effects of peroxisome proliferator-activated receptor-γ ligand troglitazone on colon cancer cell growth

作　　者：卡马尔[1] 万远廉[1] 刘玉村[1] 汪欣[1] 崔巍[1] 王春雷[1] 陈焕年[1] 王会元[1] 朱静[1] 

机构地区：[1]北京大学第一医院普通外科,北京100034

出　　处：《北京大学学报（医学版）》2006年第4期385-388,共4页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(30471683);教育部科学技术研究重点项目(02003)资助~~

摘　　要：目的:探讨过氧化物酶增殖物激活受体γ(peroxisom e proliferator-activated receptorγ-,PPARγ)在大肠癌细胞SW-480中的表达及PPARγ被其配体曲格列酮(troglitazone,TGZ)活化后对SW-480细胞生长的影响。方法:将SW-480细胞分为对照组和TGZ不同浓度(5,10,20,25μmol/L)处理组。采用免疫印迹(W estern b lot)法检测SW-480细胞中PPARγ蛋白质的表达,利用细胞计数法和3-(4,5二-甲基-2噻-唑)-2,5二-苯基溴化四唑(MTT)检测TGZ和PPARγ选择性阻断剂T0070907对SW-480细胞生长的影响,用流式细胞仪测定细胞凋亡。结果:大肠癌细胞系Lovo和HT-29中均有PPARγ高表达,SW-480细胞有相对低表达。细胞计数法和MTT法显示随着TGZ浓度的增加,TGZ对大肠癌细胞SW-480生长抑制作用也增加。各组间比较差异有统计学意义。用TGZ的不同浓度(5,10,20,25μmol/L)刺激SW-480后第48小时的抑制率分别为3.3%,8.3%,25%,29%。用流式细胞仪检测显示TGZ对SW-480细胞诱导凋亡,而且有剂量依赖关系。用TGZ刺激SW-480细胞后48 h测细胞凋亡时发现,TGZ浓度低于15μmol/L时,TGZ对SW-480细胞诱导凋亡作用弱。TGZ浓度≥20μmol/L时,诱导凋亡作用明显,与未加药组比较差异有统计学意义。TGZ浓度达25μmol/L时诱导凋亡更明显。细胞计数法显示随着PPARγ选择性阻断剂T0070907浓度的增加,对大肠癌细胞SW-480生长诱导作用也增加。不同组间比较差异有统计学意义。结论:PPARγ在大肠癌细胞Lovo,HT-29,SW-480中均有表达,PPARγ被其配体活化后可抑制大肠癌细胞的生长,诱导凋亡。ABSTRACT Objective： To investigate the expression of peroxisome proliferator-activated receptor - （PPARγ） in colon cancer cell lines and the effects of PPARγactivation by its ligand troglitazone on cell growth in SW-480 cells. Methods： PPARγexpression was detected in Lovo, HT-29 and SW-480 cells using western blot. The effects of PPARγactivation by its ligand troglitazone （TGZ） and selective antagonist T0070907 on cell growth were assessed by MTT and cell count methods; apoptosis was detected by flow cytometry method. Results： Western blot result revealed that PPARγprotein was highly expressed in Lovo and HT-29 cells and there was relatively lower expression in SW-480 cells. Cell count method and MTT revealed that activation of SW-480 cells with TGZ resulted in inhibition of growth in a dose dependent manner. The effect of anti-proliferation increased with increasing doses of TGZ. Rates of growth inhibition were 3.3%, 8.3%, 25%, and 29% for different doses 5, 10, 20 and 25 μmol/L respectively. Flow cytometry method detected apoptosis in a dose dependent manner. When the concentration of TGZ was less than 15 μmol/L , the apoptotic effect was found to be weak. The apoptotic effect was prominent when the concentration exceeded 20μmol/L. Cell count method revealed that selective antagonist of PPAR γstimulated cell growth of SW-480 cells in a dose dependent manner. Conclusion： PPAR γis expressed in colon cancer ceils. Activation of PPAR γby its ligands in colon ceils has potent anti-proliferative and pro-apoptotic effects, suggesting that PPAR γ activation by its ligands may provide therapeutic value for eoloreetal cancer oatients.

关 键 词：PPARΓ 结直肠肿瘤 酮类 

分 类 号：R735.34[医药卫生—肿瘤]